Impact of CD8 + T-cell activation on CD4 + T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy

Peter W. Hunt, Huyen L. Cao, Conrad Muzoora, Isaac Ssewanyana, John Bennett, Nneka Emenyonu, Annet Kembabazi, Torsten B. Neilands, David R. Bangsberg, Steven G. Deeks, Jeffrey N. Martin

Research output: Contribution to journalArticle

Abstract

OBJECTIVES:: To assess whether T-cell activation independently predicts the extent of CD4 T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy (ART). DESIGN:: Prospective cohort study. METHODS:: HIV-infected adults starting ART and achieving a plasma HIV RNA level (VL) less than 400 copies/ml by month 6 were sampled from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort in Mbarara, Uganda. CD4 count, VL, and the percentage-activated (CD38HLA-DR) T cells were measured every 3 months. RESULTS:: Of 451 HIV-infected Ugandans starting ART, most were women (70%) with median pre-ART values: age, 34 years; CD4 count, 135 cells/μl; and VL, 5.1 log10 copies/ml. Of these, 93% achieved a VL less than 400 copies/ml by month 6 and were followed for a median of 24 months, with 8% lost to follow-up at 3 years. Higher pre-ART CD8 T-cell activation was associated with diminished CD4 recovery after year 1, after adjustment for pre-ART CD4 count, VL, and sex (P = 0.017). Thirty-four participants died, 15 after month 6. Each 10% point increase in activated CD8 T cells at month 6 of suppressive ART was associated with a 1.6-fold increased hazard of subsequent death after adjusting for pretherapy CD4 count (P = 0.048). CONCLUSIONS:: Higher pre-ART CD8 T-cell activation independently predicts slower CD4 T-cell recovery and higher persistent CD8 T-cell activation during ART-mediated viral suppression independently predicts increased mortality among HIV-infected Ugandans. Novel therapeutic strategies aimed at preventing or reversing immune activation during ART are needed in this setting.

Original languageEnglish (US)
Pages (from-to)2123-2131
Number of pages9
JournalAIDS
Volume25
Issue number17
DOIs
StatePublished - Nov 13 2011
Externally publishedYes

Fingerprint

HIV
T-Lymphocytes
Mortality
CD4 Lymphocyte Count
Therapeutics
Uganda
Lost to Follow-Up
Acquired Immunodeficiency Syndrome
Cohort Studies
Prospective Studies
RNA

Keywords

  • Antiretroviral therapy
  • HIV
  • Mortality
  • Sub-Saharan Africa
  • T-cell activation
  • Uganda

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Hunt, P. W., Cao, H. L., Muzoora, C., Ssewanyana, I., Bennett, J., Emenyonu, N., ... Martin, J. N. (2011). Impact of CD8 + T-cell activation on CD4 + T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy. AIDS, 25(17), 2123-2131. https://doi.org/10.1097/QAD.0b013e32834c4ac1

Impact of CD8 + T-cell activation on CD4 + T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy. / Hunt, Peter W.; Cao, Huyen L.; Muzoora, Conrad; Ssewanyana, Isaac; Bennett, John; Emenyonu, Nneka; Kembabazi, Annet; Neilands, Torsten B.; Bangsberg, David R.; Deeks, Steven G.; Martin, Jeffrey N.

In: AIDS, Vol. 25, No. 17, 13.11.2011, p. 2123-2131.

Research output: Contribution to journalArticle

Hunt, PW, Cao, HL, Muzoora, C, Ssewanyana, I, Bennett, J, Emenyonu, N, Kembabazi, A, Neilands, TB, Bangsberg, DR, Deeks, SG & Martin, JN 2011, 'Impact of CD8 + T-cell activation on CD4 + T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy', AIDS, vol. 25, no. 17, pp. 2123-2131. https://doi.org/10.1097/QAD.0b013e32834c4ac1
Hunt, Peter W. ; Cao, Huyen L. ; Muzoora, Conrad ; Ssewanyana, Isaac ; Bennett, John ; Emenyonu, Nneka ; Kembabazi, Annet ; Neilands, Torsten B. ; Bangsberg, David R. ; Deeks, Steven G. ; Martin, Jeffrey N. / Impact of CD8 + T-cell activation on CD4 + T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy. In: AIDS. 2011 ; Vol. 25, No. 17. pp. 2123-2131.
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abstract = "OBJECTIVES:: To assess whether T-cell activation independently predicts the extent of CD4 T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy (ART). DESIGN:: Prospective cohort study. METHODS:: HIV-infected adults starting ART and achieving a plasma HIV RNA level (VL) less than 400 copies/ml by month 6 were sampled from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort in Mbarara, Uganda. CD4 count, VL, and the percentage-activated (CD38HLA-DR) T cells were measured every 3 months. RESULTS:: Of 451 HIV-infected Ugandans starting ART, most were women (70{\%}) with median pre-ART values: age, 34 years; CD4 count, 135 cells/μl; and VL, 5.1 log10 copies/ml. Of these, 93{\%} achieved a VL less than 400 copies/ml by month 6 and were followed for a median of 24 months, with 8{\%} lost to follow-up at 3 years. Higher pre-ART CD8 T-cell activation was associated with diminished CD4 recovery after year 1, after adjustment for pre-ART CD4 count, VL, and sex (P = 0.017). Thirty-four participants died, 15 after month 6. Each 10{\%} point increase in activated CD8 T cells at month 6 of suppressive ART was associated with a 1.6-fold increased hazard of subsequent death after adjusting for pretherapy CD4 count (P = 0.048). CONCLUSIONS:: Higher pre-ART CD8 T-cell activation independently predicts slower CD4 T-cell recovery and higher persistent CD8 T-cell activation during ART-mediated viral suppression independently predicts increased mortality among HIV-infected Ugandans. Novel therapeutic strategies aimed at preventing or reversing immune activation during ART are needed in this setting.",
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T1 - Impact of CD8 + T-cell activation on CD4 + T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy

AU - Hunt, Peter W.

AU - Cao, Huyen L.

AU - Muzoora, Conrad

AU - Ssewanyana, Isaac

AU - Bennett, John

AU - Emenyonu, Nneka

AU - Kembabazi, Annet

AU - Neilands, Torsten B.

AU - Bangsberg, David R.

AU - Deeks, Steven G.

AU - Martin, Jeffrey N.

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N2 - OBJECTIVES:: To assess whether T-cell activation independently predicts the extent of CD4 T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy (ART). DESIGN:: Prospective cohort study. METHODS:: HIV-infected adults starting ART and achieving a plasma HIV RNA level (VL) less than 400 copies/ml by month 6 were sampled from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort in Mbarara, Uganda. CD4 count, VL, and the percentage-activated (CD38HLA-DR) T cells were measured every 3 months. RESULTS:: Of 451 HIV-infected Ugandans starting ART, most were women (70%) with median pre-ART values: age, 34 years; CD4 count, 135 cells/μl; and VL, 5.1 log10 copies/ml. Of these, 93% achieved a VL less than 400 copies/ml by month 6 and were followed for a median of 24 months, with 8% lost to follow-up at 3 years. Higher pre-ART CD8 T-cell activation was associated with diminished CD4 recovery after year 1, after adjustment for pre-ART CD4 count, VL, and sex (P = 0.017). Thirty-four participants died, 15 after month 6. Each 10% point increase in activated CD8 T cells at month 6 of suppressive ART was associated with a 1.6-fold increased hazard of subsequent death after adjusting for pretherapy CD4 count (P = 0.048). CONCLUSIONS:: Higher pre-ART CD8 T-cell activation independently predicts slower CD4 T-cell recovery and higher persistent CD8 T-cell activation during ART-mediated viral suppression independently predicts increased mortality among HIV-infected Ugandans. Novel therapeutic strategies aimed at preventing or reversing immune activation during ART are needed in this setting.

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KW - HIV

KW - Mortality

KW - Sub-Saharan Africa

KW - T-cell activation

KW - Uganda

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